CHMP4A

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005635 nuclear envelope	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: nuclear envelope. Reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function. Supporting Evidence: PMID:26040713 ESCRT-III controls nuclear envelope reformation UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0031468 nuclear membrane reassembly	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: nuclear membrane reassembly. Reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function. Supporting Evidence: PMID:26040713 ESCRT-III controls nuclear envelope reformation UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0000815 ESCRT III complex	IBA GO_REF:0000033	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0009898 cytoplasmic side of plasma membrane	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: cytoplasmic side of plasma membrane. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0032511 late endosome to vacuole transport via multivesicular body sorting pathway	IBA GO_REF:0000033	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: late endosome to vacuole transport via multivesicular body sorting pathway. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0000776 kinetochore	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: kinetochore. Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. Supporting Evidence: PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 controls abscission timing through inhibition of ESCRT-III Snf7 polymerization UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0001778 plasma membrane repair	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: plasma membrane repair. Reason: Plasma membrane repair is a valid ESCRT output context, but the core CHMP4A function remains ESCRT-III membrane remodeling in endosomal/MVB and related compartments. Supporting Evidence: PMID:24482116 ESCRT proteins were recruited within seconds to plasma membrane wounds PMID:24482116 repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005643 nuclear pore	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: nuclear pore. Reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function. Supporting Evidence: PMID:26040713 ESCRT-III controls nuclear envelope reformation UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005765 lysosomal membrane	IEA GO_REF:0000117	ACCEPT	Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: lysosomal membrane. Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. Supporting Evidence: PMID:21975012 SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation PMID:17984323 Functional multivesicular bodies are required for autophagic clearance UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005828 kinetochore microtubule	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: kinetochore microtubule. Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. Supporting Evidence: PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 controls abscission timing through inhibition of ESCRT-III Snf7 polymerization UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0007034 vacuolar transport	IEA GO_REF:0000002	MODIFY	Summary: The broad vacuolar transport label is less precise than CHMP4A MVB/endosomal sorting function. Reason: CHMP4A is best represented by ESCRT-III-mediated MVB sorting and ILV/membrane fission, not generic vacuolar transport. Proposed replacements: multivesicular body sorting pathway Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0007080 mitotic metaphase chromosome alignment	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: mitotic metaphase chromosome alignment. Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. Supporting Evidence: PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 controls abscission timing through inhibition of ESCRT-III Snf7 polymerization UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0030496 midbody	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: midbody. Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. Supporting Evidence: PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 controls abscission timing through inhibition of ESCRT-III Snf7 polymerization UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0030659 cytoplasmic vesicle membrane	IEA GO_REF:0000044	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: cytoplasmic vesicle membrane. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
GO:0031468 nuclear membrane reassembly	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: nuclear membrane reassembly. Reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function. Supporting Evidence: PMID:26040713 ESCRT-III controls nuclear envelope reformation UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0031902 late endosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: late endosome membrane. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
GO:0032585 multivesicular body membrane	IEA GO_REF:0000117	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body membrane. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
GO:0036258 multivesicular body assembly	IEA GO_REF:0000117	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0039702 viral budding via host ESCRT complex	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex. Reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function. Supporting Evidence: PMID:18511562 ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0042803 protein homodimerization activity	IEA GO_REF:0000117	MODIFY	Summary: protein homodimerization activity captures CHMP4A self-association but is less accurate than ESCRT-III polymerization and membrane bending. Reason: CHMP4A forms curved ESCRT-III filaments/polymers that bend membranes; homodimer or identical-protein binding terms are weaker molecular descriptions. Proposed replacements: protein polymerization membrane bending activity Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IEA GO_REF:0000117	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0046761 viral budding from plasma membrane	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: viral budding from plasma membrane. Reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function. Supporting Evidence: PMID:18511562 ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0061952 midbody abscission	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: midbody abscission. Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. Supporting Evidence: PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 controls abscission timing through inhibition of ESCRT-III Snf7 polymerization UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0071985 multivesicular body sorting pathway	IEA GO_REF:0000117	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0097352 autophagosome maturation	IEA GO_REF:0000117	ACCEPT	Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagosome maturation. Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. Supporting Evidence: PMID:21975012 SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation PMID:17984323 Functional multivesicular bodies are required for autophagic clearance UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:1901673 regulation of mitotic spindle assembly	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: regulation of mitotic spindle assembly. Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. Supporting Evidence: PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 controls abscission timing through inhibition of ESCRT-III Snf7 polymerization UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:1902774 late endosome to lysosome transport	IEA GO_REF:0000117	ACCEPT	Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: late endosome to lysosome transport. Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. Supporting Evidence: PMID:21975012 SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation PMID:17984323 Functional multivesicular bodies are required for autophagic clearance UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:1904930 amphisome membrane	IEA GO_REF:0000117	ACCEPT	Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: amphisome membrane. Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. Supporting Evidence: PMID:21975012 SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation PMID:17984323 Functional multivesicular bodies are required for autophagic clearance UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is not informative for CHMP4A: protein binding. Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0005515 protein binding	IPI PMID:16730941 A systematic analysis of human CHMP protein interactions: ad...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is not informative for CHMP4A: protein binding. Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0005515 protein binding	IPI PMID:17350572 Structural and biochemical studies of ALIX/AIP1 and its role...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is not informative for CHMP4A: protein binding. Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0005515 protein binding	IPI PMID:18511562 ALIX-CHMP4 interactions in the human ESCRT pathway.	MARK AS OVER ANNOTATED	Summary: Generic protein binding is not informative for CHMP4A: protein binding. Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Generic protein binding is not informative for CHMP4A: protein binding. Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is not informative for CHMP4A: protein binding. Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0000421 autophagosome membrane	IDA PMID:17984323 Functional multivesicular bodies are required for autophagic...	ACCEPT	Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagosome membrane. Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. Supporting Evidence: PMID:21975012 SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation PMID:17984323 Functional multivesicular bodies are required for autophagic clearance UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0000776 kinetochore	IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: kinetochore. Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. Supporting Evidence: PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 controls abscission timing through inhibition of ESCRT-III Snf7 polymerization UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0000815 ESCRT III complex	NAS PMID:36107470 Comprehensive analysis of the human ESCRT-III-MIT domain int...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0001778 plasma membrane repair	IDA PMID:24482116 ESCRT machinery is required for plasma membrane repair.	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: plasma membrane repair. Reason: Plasma membrane repair is a valid ESCRT output context, but the core CHMP4A function remains ESCRT-III membrane remodeling in endosomal/MVB and related compartments. Supporting Evidence: PMID:24482116 ESCRT proteins were recruited within seconds to plasma membrane wounds PMID:24482116 repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005643 nuclear pore	IDA PMID:26040713 ESCRT-III controls nuclear envelope reformation.	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: nuclear pore. Reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function. Supporting Evidence: PMID:26040713 ESCRT-III controls nuclear envelope reformation UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005765 lysosomal membrane	IDA PMID:17984323 Functional multivesicular bodies are required for autophagic...	ACCEPT	Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: lysosomal membrane. Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. Supporting Evidence: PMID:21975012 SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation PMID:17984323 Functional multivesicular bodies are required for autophagic clearance UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005828 kinetochore microtubule	IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: kinetochore microtubule. Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. Supporting Evidence: PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 controls abscission timing through inhibition of ESCRT-III Snf7 polymerization UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005886 plasma membrane	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: plasma membrane. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0006914 autophagy	IMP PMID:17984323 Functional multivesicular bodies are required for autophagic...	ACCEPT	Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagy. Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. Supporting Evidence: PMID:21975012 SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation PMID:17984323 Functional multivesicular bodies are required for autophagic clearance UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0006997 nucleus organization	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: nucleus organization. Reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function. Supporting Evidence: PMID:26040713 ESCRT-III controls nuclear envelope reformation UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0007080 mitotic metaphase chromosome alignment	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: mitotic metaphase chromosome alignment. Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. Supporting Evidence: PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 controls abscission timing through inhibition of ESCRT-III Snf7 polymerization UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0030496 midbody	IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: midbody. Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. Supporting Evidence: PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 controls abscission timing through inhibition of ESCRT-III Snf7 polymerization UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0031468 nuclear membrane reassembly	IMP PMID:26040713 ESCRT-III controls nuclear envelope reformation.	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: nuclear membrane reassembly. Reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function. Supporting Evidence: PMID:26040713 ESCRT-III controls nuclear envelope reformation UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0032585 multivesicular body membrane	IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body membrane. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
GO:0036258 multivesicular body assembly	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0039702 viral budding via host ESCRT complex	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex. Reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function. Supporting Evidence: PMID:18511562 ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IDA PMID:17984323 Functional multivesicular bodies are required for autophagic...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0046761 viral budding from plasma membrane	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: viral budding from plasma membrane. Reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function. Supporting Evidence: PMID:18511562 ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0051469 vesicle fusion with vacuole	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	MODIFY	Summary: vesicle fusion with vacuole overstates a direct vesicle-fusion role for CHMP4A. Reason: CHMP4A is an ESCRT-III membrane-remodeling subunit in MVB/endolysosomal trafficking; cached evidence supports late endosome/MVB to lysosome traffic more directly than CHMP4A as a fusion effector. Proposed replacements: late endosome to lysosome transport Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0061763 multivesicular body-lysosome fusion	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	MODIFY	Summary: multivesicular body-lysosome fusion overstates a direct vesicle-fusion role for CHMP4A. Reason: CHMP4A is an ESCRT-III membrane-remodeling subunit in MVB/endolysosomal trafficking; cached evidence supports late endosome/MVB to lysosome traffic more directly than CHMP4A as a fusion effector. Proposed replacements: late endosome to lysosome transport Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0061952 midbody abscission	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: midbody abscission. Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. Supporting Evidence: PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 controls abscission timing through inhibition of ESCRT-III Snf7 polymerization UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0071985 multivesicular body sorting pathway	IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0090148 membrane fission	NAS PMID:19234443 Membrane scission by the ESCRT-III complex.	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: membrane fission. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0097352 autophagosome maturation	IMP PMID:17984323 Functional multivesicular bodies are required for autophagic...	ACCEPT	Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagosome maturation. Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. Supporting Evidence: PMID:21975012 SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation PMID:17984323 Functional multivesicular bodies are required for autophagic clearance UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:1901673 regulation of mitotic spindle assembly	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: regulation of mitotic spindle assembly. Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. Supporting Evidence: PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 controls abscission timing through inhibition of ESCRT-III Snf7 polymerization UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:1902774 late endosome to lysosome transport	IMP PMID:17984323 Functional multivesicular bodies are required for autophagic...	ACCEPT	Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: late endosome to lysosome transport. Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. Supporting Evidence: PMID:21975012 SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation PMID:17984323 Functional multivesicular bodies are required for autophagic clearance UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:1904930 amphisome membrane	IDA PMID:17984323 Functional multivesicular bodies are required for autophagic...	ACCEPT	Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: amphisome membrane. Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. Supporting Evidence: PMID:21975012 SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation PMID:17984323 Functional multivesicular bodies are required for autophagic clearance UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0050877 nervous system process	IMP PMID:21975012 ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: nervous system process. Reason: The neuron paper supports CHMP4A-dependent neuronal survival and cargo turnover, but nervous system process is a broad phenotype rather than CHMP4A core molecular/cellular function. Supporting Evidence: PMID:21975012 hSnf7-1 and hSnf7-2 are required for the survival of human neurons PMID:21975012 hSnf7-1 and hSnf7-2 may have preferred interacting partners to form distinct ESCRT-III with different cellular functions
GO:0071985 multivesicular body sorting pathway	IMP PMID:21975012 ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0000815 ESCRT III complex	IDA PMID:18209100 Plasma membrane deformation by circular arrays of ESCRT-III ...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0042802 identical protein binding	IPI PMID:18209100 Plasma membrane deformation by circular arrays of ESCRT-III ...	MODIFY	Summary: identical protein binding captures CHMP4A self-association but is less accurate than ESCRT-III polymerization and membrane bending. Reason: CHMP4A forms curved ESCRT-III filaments/polymers that bend membranes; homodimer or identical-protein binding terms are weaker molecular descriptions. Proposed replacements: protein polymerization membrane bending activity Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0051258 protein polymerization	IMP PMID:18209100 Plasma membrane deformation by circular arrays of ESCRT-III ...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: protein polymerization. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0005515 protein binding	IPI PMID:18641129 Differential requirements for Alix and ESCRT-III in cytokine...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is not informative for CHMP4A: protein binding. Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0016236 macroautophagy	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: macroautophagy. Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. Supporting Evidence: PMID:21975012 SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation PMID:17984323 Functional multivesicular bodies are required for autophagic clearance UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0000815 ESCRT III complex	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0036258 multivesicular body assembly	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0039702 viral budding via host ESCRT complex	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex. Reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function. Supporting Evidence: PMID:18511562 ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0000815 ESCRT III complex	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0005737 cytoplasm	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: cytoplasm. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: PMID:21975012 Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005768 endosome	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: endosome. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
GO:0005886 plasma membrane	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: plasma membrane. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0010324 membrane invagination	IMP PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: membrane invagination. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0030117 membrane coat	IMP PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: membrane coat. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0051258 protein polymerization	IMP PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: protein polymerization. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0039702 viral budding via host ESCRT complex	IGI PMID:24107264 ESCRT requirements for EIAV budding.	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex. Reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function. Supporting Evidence: PMID:18511562 ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005515 protein binding	IPI PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar p...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is not informative for CHMP4A: protein binding. Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0042803 protein homodimerization activity	IPI PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar p...	MODIFY	Summary: protein homodimerization activity captures CHMP4A self-association but is less accurate than ESCRT-III polymerization and membrane bending. Reason: CHMP4A forms curved ESCRT-III filaments/polymers that bend membranes; homodimer or identical-protein binding terms are weaker molecular descriptions. Proposed replacements: protein polymerization membrane bending activity Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0005515 protein binding	IPI PMID:14505570 The protein network of HIV budding.	MARK AS OVER ANNOTATED	Summary: Generic protein binding is not informative for CHMP4A: protein binding. Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0000815 ESCRT III complex	IDA PMID:21975012 ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies PMID:18209100 Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0005515 protein binding	IPI PMID:21975012 ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is not informative for CHMP4A: protein binding. Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. Supporting Evidence: UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0005634 nucleus	IDA PMID:21975012 ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: nucleus. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: PMID:21975012 Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005737 cytoplasm	IDA PMID:21975012 ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: cytoplasm. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: PMID:21975012 Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0006620 post-translational protein targeting to endoplasmic reticulum membrane	IMP PMID:21975012 ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...	REMOVE	Summary: The cited CHMP4A neuron paper does not support post-translational targeting to the ER membrane. Reason: PMID:21975012 supports CHMP4A/Snf7-1 in neuron survival, ESCRT-III cargo turnover, and autophagosome accumulation; it does not provide evidence that CHMP4A mediates ER membrane targeting. Supporting Evidence: PMID:21975012 hSnf7-1 and hSnf7-2 are required for the survival of human neurons PMID:21975012 hSnf7-1 and hSnf7-2 may have preferred interacting partners to form distinct ESCRT-III with different cellular functions
GO:0006900 vesicle budding from membrane	IMP PMID:18209100 Plasma membrane deformation by circular arrays of ESCRT-III ...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: vesicle budding from membrane. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0006900 vesicle budding from membrane	IGI PMID:18209100 Plasma membrane deformation by circular arrays of ESCRT-III ...	ACCEPT	Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: vesicle budding from membrane. Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. Supporting Evidence: UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0009898 cytoplasmic side of plasma membrane	IDA PMID:18209100 Plasma membrane deformation by circular arrays of ESCRT-III ...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: cytoplasmic side of plasma membrane. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0051117 ATPase binding	IPI PMID:18209100 Plasma membrane deformation by circular arrays of ESCRT-III ...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: ATPase binding. Reason: ATPase binding reflects VPS4 engagement with CHMP4A filaments and is useful context, but CHMP4A itself is the ESCRT-III polymerizing membrane-remodeling subunit. Supporting Evidence: PMID:18209100 Binding to a coexpressed adenosine triphosphate hydrolysis-deficient mutant of VPS4B draws these filaments together UniProt:Q9BY43 Interacts with VPS4A
GO:0097320 plasma membrane tubulation	IMP PMID:18209100 Plasma membrane deformation by circular arrays of ESCRT-III ...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: plasma membrane tubulation. Reason: Plasma membrane tubulation is a useful overexpression/model phenotype for CHMP4A filament curvature, not the normal core biological process. Supporting Evidence: UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0097320 plasma membrane tubulation	IGI PMID:18209100 Plasma membrane deformation by circular arrays of ESCRT-III ...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: plasma membrane tubulation. Reason: Plasma membrane tubulation is a useful overexpression/model phenotype for CHMP4A filament curvature, not the normal core biological process. Supporting Evidence: UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks UniProt:Q9BY43 Cytoplasmic vesicle membrane. Late endosome membrane UniProt:Q9BY43 Membrane-associated
GO:0005829 cytosol	TAS Reactome:R-HSA-3159232	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: cytosol. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: PMID:21975012 Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol	TAS Reactome:R-HSA-917693	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: cytosol. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: PMID:21975012 Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol	TAS Reactome:R-HSA-917700	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: cytosol. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: PMID:21975012 Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol	TAS Reactome:R-HSA-9668389	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: cytosol. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: PMID:21975012 Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol	TAS Reactome:R-HSA-9668395	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: cytosol. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: PMID:21975012 Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol	TAS Reactome:R-HSA-9668398	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: cytosol. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: PMID:21975012 Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol	TAS Reactome:R-HSA-9668405	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: cytosol. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: PMID:21975012 Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol	TAS Reactome:R-HSA-9668415	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: cytosol. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: PMID:21975012 Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol	TAS Reactome:R-HSA-9668419	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: cytosol. Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. Supporting Evidence: PMID:21975012 Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0030496 midbody	IDA PMID:22724069 The chromosomal passenger complex controls the function of e...	KEEP AS NON CORE	Summary: True or plausible non-core CHMP4A ESCRT context: midbody. Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. Supporting Evidence: PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 controls abscission timing through inhibition of ESCRT-III Snf7 polymerization UniProt:Q9BY43 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q9BY43 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0180020 membrane bending activity	IDA PMID:18209100 Plasma membrane deformation by circular arrays of ESCRT-III ...	NEW	Summary: New CHMP4A molecular-function annotation supported by direct ESCRT-III filament/membrane curvature evidence. Reason: PMID:18209100 directly shows CHMP4A/hSnf7-1-containing ESCRT-III filaments promote or stabilize negative membrane curvature and outward budding, making membrane bending activity more informative than generic protein binding. Supporting Evidence: UniProt:Q9BY43 believed to mediate the necessary vesicle extrusion and/or membrane fission activities PMID:18209100 form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks PMID:18209100 assemble into regular approximately 5-nm filaments that curve and self-associate PMID:18209100 proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)

📄 View Raw YAML

id: Q9BY43
gene_symbol: CHMP4A
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: CHMP4A encodes a Snf7-family core subunit of ESCRT-III. Its best-supported function is non-enzymatic ESCRT-III polymerization on endosomal/MVB and related membranes, where CHMP4A-containing filaments bend membranes and support reverse-topology budding/fission for intraluminal vesicle formation, MVB cargo sorting, and downstream endolysosomal degradation. CHMP4A also participates in autophagy/autophagosome contexts, plasma membrane repair, cytokinetic abscission, nuclear envelope repair, and viral budding as topologically related ESCRT output contexts, but those should not obscure the core ESCRT-III membrane-remodeling role.
alternative_products:
- name: '1'
  id: Q9BY43-1
- name: '2'
  id: Q9BY43-2
  sequence_note: VSP_056264
existing_annotations:
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: nuclear envelope.'
    action: KEEP_AS_NON_CORE
    reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function.
    supported_by:
    - reference_id: PMID:26040713
      supporting_text: ESCRT-III controls nuclear envelope reformation
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0031468
    label: nuclear membrane reassembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: nuclear membrane reassembly.'
    action: KEEP_AS_NON_CORE
    reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function.
    supported_by:
    - reference_id: PMID:26040713
      supporting_text: ESCRT-III controls nuclear envelope reformation
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0000815
    label: ESCRT III complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0009898
    label: cytoplasmic side of plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: cytoplasmic side of plasma membrane.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0032511
    label: late endosome to vacuole transport via multivesicular body sorting pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: late endosome to vacuole transport via multivesicular body sorting pathway.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0000776
    label: kinetochore
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: kinetochore.'
    action: KEEP_AS_NON_CORE
    reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
    supported_by:
    - reference_id: PMID:22724069
      supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III
    - reference_id: PMID:22724069
      supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0001778
    label: plasma membrane repair
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: plasma membrane repair.'
    action: KEEP_AS_NON_CORE
    reason: Plasma membrane repair is a valid ESCRT output context, but the core CHMP4A function remains ESCRT-III membrane remodeling in endosomal/MVB and related compartments.
    supported_by:
    - reference_id: PMID:24482116
      supporting_text: ESCRT proteins were recruited within seconds to plasma membrane wounds
    - reference_id: PMID:24482116
      supporting_text: repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0005643
    label: nuclear pore
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: part_of
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: nuclear pore.'
    action: KEEP_AS_NON_CORE
    reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function.
    supported_by:
    - reference_id: PMID:26040713
      supporting_text: ESCRT-III controls nuclear envelope reformation
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: lysosomal membrane.'
    action: ACCEPT
    reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic clearance
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0005828
    label: kinetochore microtubule
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: kinetochore microtubule.'
    action: KEEP_AS_NON_CORE
    reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
    supported_by:
    - reference_id: PMID:22724069
      supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III
    - reference_id: PMID:22724069
      supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0007034
    label: vacuolar transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: The broad vacuolar transport label is less precise than CHMP4A MVB/endosomal sorting function.
    action: MODIFY
    reason: CHMP4A is best represented by ESCRT-III-mediated MVB sorting and ILV/membrane fission, not generic vacuolar transport.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    proposed_replacement_terms:
    - id: GO:0071985
      label: multivesicular body sorting pathway
- term:
    id: GO:0007080
    label: mitotic metaphase chromosome alignment
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: mitotic metaphase chromosome alignment.'
    action: KEEP_AS_NON_CORE
    reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
    supported_by:
    - reference_id: PMID:22724069
      supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III
    - reference_id: PMID:22724069
      supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0030496
    label: midbody
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: midbody.'
    action: KEEP_AS_NON_CORE
    reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
    supported_by:
    - reference_id: PMID:22724069
      supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III
    - reference_id: PMID:22724069
      supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0030659
    label: cytoplasmic vesicle membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: cytoplasmic vesicle membrane.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
- term:
    id: GO:0031468
    label: nuclear membrane reassembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: nuclear membrane reassembly.'
    action: KEEP_AS_NON_CORE
    reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function.
    supported_by:
    - reference_id: PMID:26040713
      supporting_text: ESCRT-III controls nuclear envelope reformation
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: late endosome membrane.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
- term:
    id: GO:0032585
    label: multivesicular body membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body membrane.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex.'
    action: KEEP_AS_NON_CORE
    reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function.
    supported_by:
    - reference_id: PMID:18511562
      supporting_text: ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex
    - reference_id: PMID:24878737
      supporting_text: Structure of cellular ESCRT-III spirals and their relationship to HIV budding
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: protein homodimerization activity captures CHMP4A self-association but is less accurate than ESCRT-III polymerization and membrane bending.
    action: MODIFY
    reason: CHMP4A forms curved ESCRT-III filaments/polymers that bend membranes; homodimer or identical-protein binding terms are weaker molecular descriptions.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    proposed_replacement_terms:
    - id: GO:0051258
      label: protein polymerization
    - id: GO:0180020
      label: membrane bending activity
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0046761
    label: viral budding from plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: viral budding from plasma membrane.'
    action: KEEP_AS_NON_CORE
    reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function.
    supported_by:
    - reference_id: PMID:18511562
      supporting_text: ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex
    - reference_id: PMID:24878737
      supporting_text: Structure of cellular ESCRT-III spirals and their relationship to HIV budding
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0061952
    label: midbody abscission
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: midbody abscission.'
    action: KEEP_AS_NON_CORE
    reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
    supported_by:
    - reference_id: PMID:22724069
      supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III
    - reference_id: PMID:22724069
      supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0071985
    label: multivesicular body sorting pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0097352
    label: autophagosome maturation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagosome maturation.'
    action: ACCEPT
    reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic clearance
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:1901673
    label: regulation of mitotic spindle assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: regulation of mitotic spindle assembly.'
    action: KEEP_AS_NON_CORE
    reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
    supported_by:
    - reference_id: PMID:22724069
      supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III
    - reference_id: PMID:22724069
      supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:1902774
    label: late endosome to lysosome transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: late endosome to lysosome transport.'
    action: ACCEPT
    reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic clearance
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:1904930
    label: amphisome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: amphisome membrane.'
    action: ACCEPT
    reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic clearance
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  qualifier: enables
  review:
    summary: 'Generic protein binding is not informative for CHMP4A: protein binding.'
    action: MARK_AS_OVER_ANNOTATED
    reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: PMID:18511562
      supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16730941
  qualifier: enables
  review:
    summary: 'Generic protein binding is not informative for CHMP4A: protein binding.'
    action: MARK_AS_OVER_ANNOTATED
    reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: PMID:18511562
      supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17350572
  qualifier: enables
  review:
    summary: 'Generic protein binding is not informative for CHMP4A: protein binding.'
    action: MARK_AS_OVER_ANNOTATED
    reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: PMID:18511562
      supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18511562
  qualifier: enables
  review:
    summary: 'Generic protein binding is not informative for CHMP4A: protein binding.'
    action: MARK_AS_OVER_ANNOTATED
    reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: PMID:18511562
      supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: 'Generic protein binding is not informative for CHMP4A: protein binding.'
    action: MARK_AS_OVER_ANNOTATED
    reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: PMID:18511562
      supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: 'Generic protein binding is not informative for CHMP4A: protein binding.'
    action: MARK_AS_OVER_ANNOTATED
    reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: PMID:18511562
      supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0000421
    label: autophagosome membrane
  evidence_type: IDA
  original_reference_id: PMID:17984323
  qualifier: located_in
  review:
    summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagosome membrane.'
    action: ACCEPT
    reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic clearance
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0000776
    label: kinetochore
  evidence_type: IDA
  original_reference_id: PMID:26040712
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: kinetochore.'
    action: KEEP_AS_NON_CORE
    reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
    supported_by:
    - reference_id: PMID:22724069
      supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III
    - reference_id: PMID:22724069
      supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0000815
    label: ESCRT III complex
  evidence_type: NAS
  original_reference_id: PMID:36107470
  qualifier: part_of
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0001778
    label: plasma membrane repair
  evidence_type: IDA
  original_reference_id: PMID:24482116
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: plasma membrane repair.'
    action: KEEP_AS_NON_CORE
    reason: Plasma membrane repair is a valid ESCRT output context, but the core CHMP4A function remains ESCRT-III membrane remodeling in endosomal/MVB and related compartments.
    supported_by:
    - reference_id: PMID:24482116
      supporting_text: ESCRT proteins were recruited within seconds to plasma membrane wounds
    - reference_id: PMID:24482116
      supporting_text: repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0005643
    label: nuclear pore
  evidence_type: IDA
  original_reference_id: PMID:26040713
  qualifier: part_of
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: nuclear pore.'
    action: KEEP_AS_NON_CORE
    reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function.
    supported_by:
    - reference_id: PMID:26040713
      supporting_text: ESCRT-III controls nuclear envelope reformation
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IDA
  original_reference_id: PMID:17984323
  qualifier: located_in
  review:
    summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: lysosomal membrane.'
    action: ACCEPT
    reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic clearance
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0005828
    label: kinetochore microtubule
  evidence_type: IDA
  original_reference_id: PMID:26040712
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: kinetochore microtubule.'
    action: KEEP_AS_NON_CORE
    reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
    supported_by:
    - reference_id: PMID:22724069
      supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III
    - reference_id: PMID:22724069
      supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:24878737
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: plasma membrane.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: IMP
  original_reference_id: PMID:17984323
  qualifier: involved_in
  review:
    summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagy.'
    action: ACCEPT
    reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic clearance
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0006997
    label: nucleus organization
  evidence_type: IMP
  original_reference_id: PMID:20616062
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: nucleus organization.'
    action: KEEP_AS_NON_CORE
    reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function.
    supported_by:
    - reference_id: PMID:26040713
      supporting_text: ESCRT-III controls nuclear envelope reformation
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0007080
    label: mitotic metaphase chromosome alignment
  evidence_type: IMP
  original_reference_id: PMID:20616062
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: mitotic metaphase chromosome alignment.'
    action: KEEP_AS_NON_CORE
    reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
    supported_by:
    - reference_id: PMID:22724069
      supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III
    - reference_id: PMID:22724069
      supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0030496
    label: midbody
  evidence_type: IDA
  original_reference_id: PMID:26040712
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: midbody.'
    action: KEEP_AS_NON_CORE
    reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
    supported_by:
    - reference_id: PMID:22724069
      supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III
    - reference_id: PMID:22724069
      supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0031468
    label: nuclear membrane reassembly
  evidence_type: IMP
  original_reference_id: PMID:26040713
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: nuclear membrane reassembly.'
    action: KEEP_AS_NON_CORE
    reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function.
    supported_by:
    - reference_id: PMID:26040713
      supporting_text: ESCRT-III controls nuclear envelope reformation
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0032585
    label: multivesicular body membrane
  evidence_type: IDA
  original_reference_id: PMID:16554368
  qualifier: located_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body membrane.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: NAS
  original_reference_id: PMID:16505166
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: IDA
  original_reference_id: PMID:24878737
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex.'
    action: KEEP_AS_NON_CORE
    reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function.
    supported_by:
    - reference_id: PMID:18511562
      supporting_text: ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex
    - reference_id: PMID:24878737
      supporting_text: Structure of cellular ESCRT-III spirals and their relationship to HIV budding
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IDA
  original_reference_id: PMID:17984323
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0046761
    label: viral budding from plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:24878737
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: viral budding from plasma membrane.'
    action: KEEP_AS_NON_CORE
    reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function.
    supported_by:
    - reference_id: PMID:18511562
      supporting_text: ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex
    - reference_id: PMID:24878737
      supporting_text: Structure of cellular ESCRT-III spirals and their relationship to HIV budding
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0051469
    label: vesicle fusion with vacuole
  evidence_type: NAS
  original_reference_id: PMID:16505166
  qualifier: involved_in
  review:
    summary: vesicle fusion with vacuole overstates a direct vesicle-fusion role for CHMP4A.
    action: MODIFY
    reason: CHMP4A is an ESCRT-III membrane-remodeling subunit in MVB/endolysosomal trafficking; cached evidence supports late endosome/MVB to lysosome traffic more directly than CHMP4A as a fusion effector.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    proposed_replacement_terms:
    - id: GO:1902774
      label: late endosome to lysosome transport
- term:
    id: GO:0061763
    label: multivesicular body-lysosome fusion
  evidence_type: NAS
  original_reference_id: PMID:16505166
  qualifier: involved_in
  review:
    summary: multivesicular body-lysosome fusion overstates a direct vesicle-fusion role for CHMP4A.
    action: MODIFY
    reason: CHMP4A is an ESCRT-III membrane-remodeling subunit in MVB/endolysosomal trafficking; cached evidence supports late endosome/MVB to lysosome traffic more directly than CHMP4A as a fusion effector.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    proposed_replacement_terms:
    - id: GO:1902774
      label: late endosome to lysosome transport
- term:
    id: GO:0061952
    label: midbody abscission
  evidence_type: IMP
  original_reference_id: PMID:20616062
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: midbody abscission.'
    action: KEEP_AS_NON_CORE
    reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
    supported_by:
    - reference_id: PMID:22724069
      supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III
    - reference_id: PMID:22724069
      supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0071985
    label: multivesicular body sorting pathway
  evidence_type: IDA
  original_reference_id: PMID:16554368
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0090148
    label: membrane fission
  evidence_type: NAS
  original_reference_id: PMID:19234443
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: membrane fission.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0097352
    label: autophagosome maturation
  evidence_type: IMP
  original_reference_id: PMID:17984323
  qualifier: involved_in
  review:
    summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagosome maturation.'
    action: ACCEPT
    reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic clearance
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:1901673
    label: regulation of mitotic spindle assembly
  evidence_type: IMP
  original_reference_id: PMID:20616062
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: regulation of mitotic spindle assembly.'
    action: KEEP_AS_NON_CORE
    reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
    supported_by:
    - reference_id: PMID:22724069
      supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III
    - reference_id: PMID:22724069
      supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:1902774
    label: late endosome to lysosome transport
  evidence_type: IMP
  original_reference_id: PMID:17984323
  qualifier: involved_in
  review:
    summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: late endosome to lysosome transport.'
    action: ACCEPT
    reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic clearance
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:1904930
    label: amphisome membrane
  evidence_type: IDA
  original_reference_id: PMID:17984323
  qualifier: located_in
  review:
    summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: amphisome membrane.'
    action: ACCEPT
    reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic clearance
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0050877
    label: nervous system process
  evidence_type: IMP
  original_reference_id: PMID:21975012
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: nervous system process.'
    action: KEEP_AS_NON_CORE
    reason: The neuron paper supports CHMP4A-dependent neuronal survival and cargo turnover, but nervous system process is a broad phenotype rather than CHMP4A core molecular/cellular function.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: hSnf7-1 and hSnf7-2 are required for the survival of human neurons
    - reference_id: PMID:21975012
      supporting_text: hSnf7-1 and hSnf7-2 may have preferred interacting partners to form distinct ESCRT-III with different cellular functions
- term:
    id: GO:0071985
    label: multivesicular body sorting pathway
  evidence_type: IMP
  original_reference_id: PMID:21975012
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0000815
    label: ESCRT III complex
  evidence_type: IDA
  original_reference_id: PMID:18209100
  qualifier: part_of
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:18209100
  qualifier: enables
  review:
    summary: identical protein binding captures CHMP4A self-association but is less accurate than ESCRT-III polymerization and membrane bending.
    action: MODIFY
    reason: CHMP4A forms curved ESCRT-III filaments/polymers that bend membranes; homodimer or identical-protein binding terms are weaker molecular descriptions.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    proposed_replacement_terms:
    - id: GO:0051258
      label: protein polymerization
    - id: GO:0180020
      label: membrane bending activity
- term:
    id: GO:0051258
    label: protein polymerization
  evidence_type: IMP
  original_reference_id: PMID:18209100
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: protein polymerization.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18641129
  qualifier: enables
  review:
    summary: 'Generic protein binding is not informative for CHMP4A: protein binding.'
    action: MARK_AS_OVER_ANNOTATED
    reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: PMID:18511562
      supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: macroautophagy.'
    action: ACCEPT
    reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic clearance
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0000815
    label: ESCRT III complex
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: part_of
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex.'
    action: KEEP_AS_NON_CORE
    reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function.
    supported_by:
    - reference_id: PMID:18511562
      supporting_text: ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex
    - reference_id: PMID:24878737
      supporting_text: Structure of cellular ESCRT-III spirals and their relationship to HIV budding
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0000815
    label: ESCRT III complex
  evidence_type: IDA
  original_reference_id: PMID:24878737
  qualifier: part_of
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:24878737
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: cytoplasm.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IDA
  original_reference_id: PMID:24878737
  qualifier: colocalizes_with
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: endosome.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:24878737
  qualifier: colocalizes_with
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: plasma membrane.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0010324
    label: membrane invagination
  evidence_type: IMP
  original_reference_id: PMID:24878737
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: membrane invagination.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0030117
    label: membrane coat
  evidence_type: IMP
  original_reference_id: PMID:24878737
  qualifier: part_of
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: membrane coat.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0051258
    label: protein polymerization
  evidence_type: IMP
  original_reference_id: PMID:24878737
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: protein polymerization.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: IGI
  original_reference_id: PMID:24107264
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex.'
    action: KEEP_AS_NON_CORE
    reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function.
    supported_by:
    - reference_id: PMID:18511562
      supporting_text: ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex
    - reference_id: PMID:24878737
      supporting_text: Structure of cellular ESCRT-III spirals and their relationship to HIV budding
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14519844
  qualifier: enables
  review:
    summary: 'Generic protein binding is not informative for CHMP4A: protein binding.'
    action: MARK_AS_OVER_ANNOTATED
    reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: PMID:18511562
      supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IPI
  original_reference_id: PMID:14519844
  qualifier: enables
  review:
    summary: protein homodimerization activity captures CHMP4A self-association but is less accurate than ESCRT-III polymerization and membrane bending.
    action: MODIFY
    reason: CHMP4A forms curved ESCRT-III filaments/polymers that bend membranes; homodimer or identical-protein binding terms are weaker molecular descriptions.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    proposed_replacement_terms:
    - id: GO:0051258
      label: protein polymerization
    - id: GO:0180020
      label: membrane bending activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14505570
  qualifier: enables
  review:
    summary: 'Generic protein binding is not informative for CHMP4A: protein binding.'
    action: MARK_AS_OVER_ANNOTATED
    reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: PMID:18511562
      supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0000815
    label: ESCRT III complex
  evidence_type: IDA
  original_reference_id: PMID:21975012
  qualifier: part_of
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
    - reference_id: PMID:18209100
      supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21975012
  qualifier: enables
  review:
    summary: 'Generic protein binding is not informative for CHMP4A: protein binding.'
    action: MARK_AS_OVER_ANNOTATED
    reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
    - reference_id: PMID:18511562
      supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:21975012
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: nucleus.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:21975012
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: cytoplasm.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
- term:
    id: GO:0006620
    label: post-translational protein targeting to endoplasmic reticulum membrane
  evidence_type: IMP
  original_reference_id: PMID:21975012
  qualifier: involved_in
  review:
    summary: The cited CHMP4A neuron paper does not support post-translational targeting to the ER membrane.
    action: REMOVE
    reason: PMID:21975012 supports CHMP4A/Snf7-1 in neuron survival, ESCRT-III cargo turnover, and autophagosome accumulation; it does not provide evidence that CHMP4A mediates ER membrane targeting.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: hSnf7-1 and hSnf7-2 are required for the survival of human neurons
    - reference_id: PMID:21975012
      supporting_text: hSnf7-1 and hSnf7-2 may have preferred interacting partners to form distinct ESCRT-III with different cellular functions
- term:
    id: GO:0006900
    label: vesicle budding from membrane
  evidence_type: IMP
  original_reference_id: PMID:18209100
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: vesicle budding from membrane.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0006900
    label: vesicle budding from membrane
  evidence_type: IGI
  original_reference_id: PMID:18209100
  qualifier: involved_in
  review:
    summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: vesicle budding from membrane.'
    action: ACCEPT
    reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- term:
    id: GO:0009898
    label: cytoplasmic side of plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:18209100
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: cytoplasmic side of plasma membrane.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0051117
    label: ATPase binding
  evidence_type: IPI
  original_reference_id: PMID:18209100
  qualifier: enables
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: ATPase binding.'
    action: KEEP_AS_NON_CORE
    reason: ATPase binding reflects VPS4 engagement with CHMP4A filaments and is useful context, but CHMP4A itself is the ESCRT-III polymerizing membrane-remodeling subunit.
    supported_by:
    - reference_id: PMID:18209100
      supporting_text: Binding to a coexpressed adenosine triphosphate hydrolysis-deficient mutant of VPS4B draws these filaments together
    - reference_id: UniProt:Q9BY43
      supporting_text: Interacts with VPS4A
- term:
    id: GO:0097320
    label: plasma membrane tubulation
  evidence_type: IMP
  original_reference_id: PMID:18209100
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: plasma membrane tubulation.'
    action: KEEP_AS_NON_CORE
    reason: Plasma membrane tubulation is a useful overexpression/model phenotype for CHMP4A filament curvature, not the normal core biological process.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0097320
    label: plasma membrane tubulation
  evidence_type: IGI
  original_reference_id: PMID:18209100
  qualifier: involved_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: plasma membrane tubulation.'
    action: KEEP_AS_NON_CORE
    reason: Plasma membrane tubulation is a useful overexpression/model phenotype for CHMP4A filament curvature, not the normal core biological process.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: UniProt:Q9BY43
      supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane
    - reference_id: UniProt:Q9BY43
      supporting_text: Membrane-associated
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3159232
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-917693
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-917700
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9668389
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9668395
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9668398
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9668405
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9668415
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9668419
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.'
    action: KEEP_AS_NON_CORE
    reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
- term:
    id: GO:0030496
    label: midbody
  evidence_type: IDA
  original_reference_id: PMID:22724069
  qualifier: located_in
  review:
    summary: 'True or plausible non-core CHMP4A ESCRT context: midbody.'
    action: KEEP_AS_NON_CORE
    reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
    supported_by:
    - reference_id: PMID:22724069
      supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III
    - reference_id: PMID:22724069
      supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
    - reference_id: UniProt:Q9BY43
      supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
    - reference_id: UniProt:Q9BY43
      supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
- term:
    id: GO:0180020
    label: membrane bending activity
  evidence_type: IDA
  original_reference_id: PMID:18209100
  qualifier: enables
  review:
    summary: New CHMP4A molecular-function annotation supported by direct ESCRT-III filament/membrane curvature evidence.
    action: NEW
    reason: PMID:18209100 directly shows CHMP4A/hSnf7-1-containing ESCRT-III filaments promote or stabilize negative membrane curvature and outward budding, making membrane bending activity more informative than generic protein binding.
    supported_by:
    - reference_id: UniProt:Q9BY43
      supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
    - reference_id: PMID:18209100
      supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
    - reference_id: PMID:19234443
      supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
    - reference_id: PMID:18209100
      supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
    - reference_id: PMID:18209100
      supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:14505570
  title: The protein network of HIV budding.
  findings: []
- id: PMID:14519844
  title: Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins.
  findings: []
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
- id: PMID:16505166
  title: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1.
  findings: []
- id: PMID:16554368
  title: The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor.
  findings: []
- id: PMID:16730941
  title: 'A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex.'
  findings: []
- id: PMID:17350572
  title: Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding.
  findings: []
- id: PMID:17984323
  title: Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease.
  findings: []
- id: PMID:18209100
  title: Plasma membrane deformation by circular arrays of ESCRT-III protein filaments.
  findings: []
- id: PMID:18511562
  title: ALIX-CHMP4 interactions in the human ESCRT pathway.
  findings: []
- id: PMID:18641129
  title: Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release.
  findings: []
- id: PMID:19234443
  title: Membrane scission by the ESCRT-III complex.
  findings: []
- id: PMID:20588296
  title: 'Membrane budding and scission by the ESCRT machinery: it''s all in the neck.'
  findings: []
- id: PMID:20616062
  title: Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance.
  findings: []
- id: PMID:21975012
  title: ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate transmembrane cargos in hESC-derived human neurons.
  findings: []
- id: PMID:22724069
  title: The chromosomal passenger complex controls the function of endosomal sorting complex required for transport-III Snf7 proteins during cytokinesis.
  findings: []
- id: PMID:24107264
  title: ESCRT requirements for EIAV budding.
  findings: []
- id: PMID:24482116
  title: ESCRT machinery is required for plasma membrane repair.
  findings: []
- id: PMID:24878737
  title: Structure of cellular ESCRT-III spirals and their relationship to HIV budding.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:26040712
  title: Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing.
  findings: []
- id: PMID:26040713
  title: ESCRT-III controls nuclear envelope reformation.
  findings: []
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
  findings: []
- id: PMID:36107470
  title: Comprehensive analysis of the human ESCRT-III-MIT domain interactome reveals new cofactors for cytokinetic abscission.
  findings: []
- id: Reactome:R-HSA-3159232
  title: Recruitment Of HIV Virion Budding Machinery
  findings: []
- id: Reactome:R-HSA-917693
  title: ESCRT Disassembly
  findings: []
- id: Reactome:R-HSA-917700
  title: MVB Vesicle Formation
  findings: []
- id: Reactome:R-HSA-9668389
  title: VPS4 binds ESCRT-III assemblies at nuclear envelope (NE) fenestrations
  findings: []
- id: Reactome:R-HSA-9668395
  title: CHMP7 binds CC2D1B
  findings: []
- id: Reactome:R-HSA-9668398
  title: CHMP7 binds CHMP4B, which recruits other subunits of the ESCRT-III complex
  findings: []
- id: Reactome:R-HSA-9668405
  title: SPAST (spastin) binds the IST1 subunit of ESCRT-III at the sites of microtubule attachment to chromatin
  findings: []
- id: Reactome:R-HSA-9668415
  title: VPS4 mediates disassembly of ESCRTIII subunits to promote sealing of holes in the nuclear envelope
  findings: []
- id: Reactome:R-HSA-9668419
  title: SPAST (spastin) mediates the severing of microtubules at chromosome attachment sites
  findings: []
- id: UniProt:Q9BY43
  title: UniProt entry for CHMP4A (Q9BY43)
  findings:
  - statement: CHMP4A is a probable core ESCRT-III component involved in MVB formation, endosomal cargo sorting, membrane fission, and exosomal release.
- id: file:human/CHMP4A/CHMP4A-notes.md
  title: Local curation notes for CHMP4A
  findings:
  - statement: Local synthesis identifies ESCRT-III polymerization/membrane bending and MVB/endosomal sorting as core CHMP4A functions, with autophagy and other ESCRT outputs retained in context.
core_functions:
- molecular_function:
    id: GO:0180020
    label: membrane bending activity
  description: CHMP4A/Snf7-1 is a core ESCRT-III structural subunit that polymerizes into curved membrane-associated filaments and promotes or stabilizes negative membrane curvature for reverse-topology budding/fission.
  in_complex:
    id: GO:0000815
    label: ESCRT III complex
  directly_involved_in:
  - id: GO:0090148
    label: membrane fission
  - id: GO:0006900
    label: vesicle budding from membrane
  locations:
  - id: GO:0031902
    label: late endosome membrane
  - id: GO:0032585
    label: multivesicular body membrane
  supported_by:
  - reference_id: UniProt:Q9BY43
    supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities
  - reference_id: PMID:18209100
    supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
  - reference_id: PMID:19234443
    supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks
  - reference_id: PMID:18209100
    supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate
  - reference_id: PMID:18209100
    supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
- description: CHMP4A-containing ESCRT-III assemblies mediate MVB intraluminal vesicle formation and ubiquitin-dependent endosomal cargo sorting toward endolysosomal degradation.
  in_complex:
    id: GO:0000815
    label: ESCRT III complex
  directly_involved_in:
  - id: GO:0071985
    label: multivesicular body sorting pathway
  - id: GO:0036258
    label: multivesicular body assembly
  - id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  locations:
  - id: GO:0032585
    label: multivesicular body membrane
  - id: GO:0005768
    label: endosome
  supported_by:
  - reference_id: UniProt:Q9BY43
    supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
  - reference_id: UniProt:Q9BY43
    supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
  - reference_id: PMID:18209100
    supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
  - reference_id: PMID:18209100
    supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
- description: CHMP4A/Snf7-1 contributes to autophagy/autophagosome maturation contexts as part of ESCRT-dependent endolysosomal membrane remodeling; direct human-neuron knockdown causes autophagosome accumulation.
  in_complex:
    id: GO:0000815
    label: ESCRT III complex
  directly_involved_in:
  - id: GO:0097352
    label: autophagosome maturation
  - id: GO:0016236
    label: macroautophagy
  locations:
  - id: GO:0000421
    label: autophagosome membrane
  - id: GO:1904930
    label: amphisome membrane
  - id: GO:0005765
    label: lysosomal membrane
  supported_by:
  - reference_id: PMID:21975012
    supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
  - reference_id: PMID:17984323
    supporting_text: Functional multivesicular bodies are required for autophagic clearance
proposed_new_terms: []
suggested_questions:
- question: Which CHMP4 paralog, CHMP4A, CHMP4B, or CHMP4C, is the dominant Snf7-family subunit during human phagophore closure and autophagosome maturation?
- question: Should GO annotations distinguish direct CHMP4A membrane-bending/polymer function from broader ESCRT output processes such as viral budding, plasma membrane repair, and nuclear envelope sealing?
- question: Does CHMP4A preferentially pair with CHMP2A in autophagy and endosomal cargo sorting, as suggested by human-neuron cargo turnover assays?
suggested_experiments:
- description: Use endogenous CHMP4A tagging and acute CHMP4A depletion/rescue during starvation-induced autophagy to image recruitment to phagophores, autophagosomes, and amphisomes.
  hypothesis: If CHMP4A directly participates in autophagosome maturation or closure, it should be transiently recruited to autophagy membranes and rescue should require its polymerization/membrane-binding region.
- description: Compare wild-type CHMP4A with ALIX-binding and C-terminal autoinhibition mutants in MVB cargo sorting, ESCRT spiral formation, plasma membrane repair, and viral budding assays.
  hypothesis: CHMP4A polymerization and partner recruitment requirements differ across endogenous ESCRT outputs and virus-hijacked budding.
- description: Biochemically reconstitute CHMP4A-containing human ESCRT-III polymers with CHMP2A/CHMP3/VPS4 and test membrane bending/scission on defined liposomes.
  hypothesis: CHMP4A contributes Snf7-family filament curvature that can drive membrane bending and support reverse-topology scission in a minimal human ESCRT-III module.

Gene Description

Existing Annotations Review

Core Functions

CHMP4A/Snf7-1 is a core ESCRT-III structural subunit that polymerizes into curved membrane-associated filaments and promotes or stabilizes negative membrane curvature for reverse-topology budding/fission.

CHMP4A-containing ESCRT-III assemblies mediate MVB intraluminal vesicle formation and ubiquitin-dependent endosomal cargo sorting toward endolysosomal degradation.

CHMP4A/Snf7-1 contributes to autophagy/autophagosome maturation contexts as part of ESCRT-dependent endolysosomal membrane remodeling; direct human-neuron knockdown causes autophagosome accumulation.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

CHMP4A notes

Local evidence reviewed

Curation synthesis

Pn Notes

CHMP4A PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | ESCRT-III complex component

PN row 2: Autophagy-Lysosome Pathway | Microautophagy | General microautophagy machinery | ESCRT-III complex component

Projected GO annotations (3)

Note

📄 View Raw YAML